The effect of phthalates exposure during pregnancy on asthma in infants aged 0 to 36 months: a birth cohort study

Authors：Jian-Qing Wang, Chun-Mei Liang, Ya-Bin Hu, Xun Xia , Zhi-Juan Li, Hui Gao, Jie Sheng, Kun Huang, Su-Fang Wang, Peng Zhu, Jia-Hu Hao, Fang-Biao Tao

Source：Environ Geochem Health. 2023 May;45(5):1951-1974

DOI: 10.1007/s10653-022-01320-x 

Abstract：

This cohort study sought to investigate the effects of phthalates exposure during pregnancy on offspring asthma and its association with placental stress and inflammatory factor mRNA expression levels. A total of 3474 pregnant women from the China Ma'anshan birth cohort participated in this study. Seven phthalate metabolites were detected in urine samples during pregnancy by solid phase extraction-high-performance liquid chromatography tandem mass spectrometry. Placenta stress and inflammation mRNA expression were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). Early pregnancy may be the critical period when phthalates exposure increases the risk of asthma in infants and young children, and there is a certain gender difference in the risk of asthma in infants and young children. Moreover, through the placenta stress and inflammatory factor associated with infant asthma found anti-inflammatory factor of interleukin-10 (IL-10) mRNA expression will reduce the risk of 36-month-old male infant asthma. The expression of interleukin-4(IL-4) and macrophage (M2) biomarker cluster of differentiation 206(CD206) mRNA reduced the risk of asthma in 18-month-old female infants. Placental stress and inflammatory response were analyzed using mediating effects. Tumor necrosis factor-α (TNFα) showed a complete mediating effect between mono-benzyl phthalate (MBzP) exposure in early pregnancy and asthma in 12-month-old males, and IL-10 also showed a complete mediating effect between mono-n-butyl phthalate (MBP) exposure in early and late pregnancy and asthma in 36-month-old males. In summary, exposure to phthalates during pregnancy may contribute to the development of asthma in infants, which may be associated with placental stress and inflammation.

中文摘要：

这项队列研究旨在调查怀孕期间接触邻苯二甲酸酯对后代哮喘的影响及其与胎盘应激和炎症因子mRNA表达水平的关联。共有来自中国马鞍山出生队列的3474名孕妇参加了这项研究。采用固相萃取-高效液相色谱串联质谱法检测孕期尿样中10种邻苯二甲酸酯代谢物。通过实时定量聚合酶链反应（RT-qPCR）评估胎盘应激和炎症mRNA表达。妊娠早期可能是邻苯二甲酸酯暴露增加婴幼儿哮喘风险的关键时期，婴幼儿哮喘风险存在一定的性别差异。而且，通过胎盘应激和与婴儿哮喘相关的炎症因子发现抗炎因子白细胞介素-10（IL-36）mRNA的表达将降低4个月大的男婴哮喘的风险。分化4（CD2）mRNA的白细胞介素-206（IL-206）和巨噬细胞（M18）生物标志物簇的表达降低了12月龄女婴患哮喘的风险。使用中介效应分析胎盘应激和炎症反应。肿瘤坏死因子-α（TNFα）在妊娠早期邻苯二甲酸单苄酯（MBzP）暴露与10月龄男性哮喘之间表现出完全的介导作用，IL-36在妊娠早期和晚期邻苯二甲酸单正丁酯（MBP）暴露与36月龄男性哮喘之间也表现出完全的介导作用。总之，怀孕期间接触邻苯二甲酸酯可能会导致婴儿哮喘的发展，这可能与胎盘压力和炎症有关。

关键字：哮喘；炎症mRNA；邻苯二甲酸酯；胎盘压力；怀孕。